Cardiovascular Effects of Angiotensin-(1-7) in Obesity Hypertension

Obesity is a global health concern that is associated with high blood pressure and an increased risk for developing cardiovascular disease. The purpose of this study is to find out if the investigational drug angiotensin-(1-7) can improve cardiovascular health in people with obesity and high blood pressure.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Obesity
• Intervention / Treatment: Drug: Angiotensin-(1-7); Drug: Saline

Detailed Description

A randomized, double blind, placebo controlled, crossover study will be conducted to determine if acute intravenous angiotensin-(1-7) infusion reduces cardiovascular sympathetic tone and blood pressure and improves the function of blood vessels in participants with obesity hypertension. This is an outpatient study that requires a screening visit, and if eligible, two study visits separated by at least one week in the Clinical Research Center within the Penn State Milton S. Hershey Medical Center. The study visits will include intravenous infusion of angiotensin-(1-7) or saline for approximately two hours, starting with increasing doses and holding at a steady-state dose. Endothelial function will be measured and blood samples collected at baseline and at the end of infusion. Blood pressure, heart rate, and muscle sympathetic nerve activity (via microneurography) will be measured continuously throughout the study. Each study visit will last approximately 4 hours.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Aimee Cauffman, RN; Phone Number: 717-531-1617; Email: acauffman@pennstatehealth.psu.edu
• Study Contact Backup: Name: Amy Arnold, PhD; Phone Number: 717-531-3674; Email: aarnold5@pennstatehealth.psu.edu

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State Milton S. Hershey Medical Center
      • Sub-Investigator: Urs A Leuenberger, MD
      • Sub-Investigator: Aimee Cauffman, RN
      • Sub-Investigator: Cheryl Blaha, RN
      • Sub-Investigator: Jian Cui, PhD
      • Contact: Amy Arnold, PhD; Phone Number: 717-531-3674; Email: aarnold5@pennstatehealth.psu.edu
      • Sub-Investigator: Takuto Hamaoka, MD, PhD
      • Sub-Investigator: Mami Hamaoka, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women of all races
• Age 18 to 65 years
• Body mass index (BMI) between 30-45 kg/m2
• Pre-hypertension (defined as two or more seated blood pressure readings >120/80 mmHg) or hypertension (defined as two or more seated blood pressure readings >130/80 mmHg or use of antihypertensive medications)
• Capable of giving informed consent
• Fluent in written and spoken English
• Satisfactory history and physical exam

Exclusion Criteria:

• Age ≤ 17 or ≥ 66 years
• Taking more than two antihypertensive medications
• Secondary causes of hypertension (e.g., pheochromocytoma, primary aldosteronism, aortic coarctation, adrenal disease)
• Pregnant or nursing women
• Women taking hormone replacement therapy within 6 months
• Decisional impairment
• Prisoners
• Alcohol or drug abuse
• Current smokers
• Highly trained athletes
• Subjects with >5% weight change in the past 3 months
• BMI > 45 kg/m2
• Evidence of type I or type II diabetes (fasting glucose > 126 mg/dL or use of anti-diabetic medications)
• History of serious cardiovascular disease (e.g. myocardial infarction within 6 months, symptomatic coronary artery disease, presence of angina pectoris, significant arrhythmia, congestive heart failure, deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, hypertrophic cardiomyopathy) or cerebrovascular disease (e.g. cerebral hemorrhage, stroke, transient Ischemic attack)
• History or presence of immunological or hematological disorders
• Impaired hepatic function [aspartate aminotransferase (AST) or alanine transaminase (ALT) levels >2 times upper limit of normal range]
• Impaired renal function (serum creatinine >2.0 mg/dl)
• Anemia
• Treatment with drugs increasing sympathetic activity [e.g., serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors, stimulants]
• Treatment with phosphodiesterase-5 inhibitors
• Treatment with anticoagulants (e.g. warfarin)
• Treatment with chronic systemic glucocorticoid therapy (>7 consecutive days in 1 month)
• Treatment with any investigational drug in the 1-month preceding the study
• Inability to give, or withdraw, informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Angiotensin-(1-7); Participants will receive intravenous angiotensin-(1-7) at one study visit for a total of 120 minutes. Angiotensin-(1-7) will be given in escalating doses of 2 ng/kg/min, 4 ng/kg/min, and 8 ng/kg/min. Each of these doses will be infused for 10 minutes. Following this 30 minute dose escalation period, angiotensin-(1-7) will be given at 8 ng/kg/min for an additional 90 minutes. Infusion rates will be calculated for each patient based on body mass.	Drug: Angiotensin-(1-7); This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.; Other Names: Angiotensin I/II (1-7) Acetate
Placebo Comparator: Saline; Participants receive intravenous saline at one study visit for a total of 120 minutes. The volume of saline will match the volume of angiotensin-(1-7) infused. Infusion rates will be calculated for each patient based on body mass.	Drug: Saline; Saline will be used as the placebo comparator.; Other Names: Normal saline; 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Muscle Sympathetic Nerve Burst Rate	Muscle sympathetic nerve burst rate will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Brachial Artery Diameter	A blood pressure cuff will be inflated to a suprasystolic pressure for 5 minutes then deflated. Brachial artery diameter will be measured continuously before, during, and after cuff inflation using duplex ultrasound at baseline and at the end of angiotensin-(1-7) versus saline infusion.	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Muscle Sympathetic Nerve Burst Incidence	Muscle sympathetic nerve burst incidence will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Muscle Sympathetic Nerve Amplitude	Muscle sympathetic nerve amplitude will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Muscle Sympathetic Nerve Total Activity	Muscle sympathetic nerve total activity will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Systolic Blood Pressure	Blood pressure will be measured continuously with a finger and arm cuff during angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Diastolic Blood Pressure	Blood pressure will be measured continuously with a finger and arm cuff during angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Heart Rate	Heart rate will be measured continuously by electrocardiogram during angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Plasma Catecholamines	Circulating catecholamine levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.	120 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Angiotensin II	Plasma angiotensin II levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Angiotensin-(1-7)	Plasma angiotensin-(1-7) levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Renin Activity	Plasma renin activity will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Aldosterone	Plasma or serum aldosterone levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Heart Rate Variability	Heart rate variability will be calculated from the continuous electrocardiogram recordings obtained during angiotensin-(1-7) versus saline infusion.	120 minutes
Change in Baroreflex Sensitivity	Baroreflex sensitivity will be calculated from the continuous blood pressure and electrocardiogram recordings obtained during angiotensin-(1-7) versus saline infusion.	120 minutes

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Amy Arnold, PhD, Pennsylvania State University College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Angiotensin-(1-7); Endothelial Function; Cardiovascular; Blood Pressure; Sympathetic Nervous System
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Hypertension; Organic Chemicals; Pharmaceutical Preparations; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Inorganic Chemicals; Chlorine Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Fatty Acids, Volatile; Sodium Compounds; Chlorides; Hydrochloric Acid; Saline Solution; Sodium Chloride; Acetates; angiotensin I (1-7)
• Other Study ID Numbers: STUDY 8170-Part 2; R01HL170140 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No